Mitochondrial targeting drug lonidamine triggered apoptosis in doxorubicin-resistant HepG2 cells
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AbstractMitochondria play a crucial role in the induction and execution of apoptosis. Accordingly, recent suggestions have been made to use agents that directly act on mitochondria to trigger apoptosis so that drug-sensitive and-resistant tumour cells can be eliminated. To test this hypothesis, human hepatocarcinoma HepG2 and its derivative R-HepG2 with doxorubicin (Dox) resistance as a result of expression of P-glycoprotein were used to investigate the effect of lonidamine (LND), a new mitochondrial targeting drug, on the induction of apoptosis. Results from our study indicate that R-HepG2 cells were more sensitive to LND than parental cells in terms of cytotoxicity determined by alamar blue assay. Cell death induced by LND was associated with the hallmarks of apoptosis such as mitochondrial membrane depolarization, release of cytochrome c, phosphatidyl-serine externalization and DNA fragmentation. Moreover, combined treatment of cells with Dox and LND elicited more cell death. Taken together, our results suggest a potential use of LND as an anti-cancer drug to bypass drug resistance and to trigger tumour destruction through apoptosis in HepG2 and R-HepG2 cells. (C) 2002 Elsevier Science Inc. All rights reserved.
All Author(s) ListLi YC, Fung KP, Kwok TT, Lee CY, Suen YK, Kong SK
Journal nameLife Sciences
Year2002
Month10
Day25
Volume Number71
Issue Number23
PublisherPERGAMON-ELSEVIER SCIENCE LTD
Pages2729 - 2740
ISSN0024-3205
eISSN1879-0631
LanguagesEnglish-United Kingdom
Keywordsapoptosis; drug resistance; lonidamine; mitochondrial; P-glycoprotein
Web of Science Subject CategoriesMedicine, Research & Experimental; MEDICINE, RESEARCH & EXPERIMENTAL; Pharmacology & Pharmacy; PHARMACOLOGY & PHARMACY; Research & Experimental Medicine

Last updated on 2020-18-10 at 01:24